The need to tailor release-rate profiles from polymeric microspheres remains one of the leading challenges in controlled drug delivery. Microsphere size, which has a significant effect on drug release rate, can potentially be varied to design a controlled drug delivery system with desired release profile. In addition, drug release rate from polymeric microspheres is dependent on material properties such as polymer molecular weight. Mathematical modeling provides insight into the fundamental processes that govern the release, and once validated with experimental results, it can be used to tailor a desired controlled drug delivery system. To these ends, PLG microspheres were fabricated using the oil-in-water emulsion technique. A quantitative study that describes the size distribution of poly(lactide-coglycolide) (PLG) microspheres is presented. A fluid mechanics-based correlation that predicts the mean microsphere diameter is formulated based on the theory of emulsification in turbulent flow. The effects of microspheres’ mean diameter, polydispersity, and polymer molecular weight on therapeutic drug release rate from poly(lactide-co-glycolide) (PLG) microspheres were investigated experimentally. Based on the experimental results, a suitable mathematical theory has been developed that incorporates the effect of microsphere size distribution and polymer degradation on drug release. In addition, a numerical optimization technique, based on the least squares method, was developed to achieve desired therapeutic drug release profiles by combining individual microsphere populations. The fluid mechanics-based mathematical correlation that predicts microsphere mean diameter provided a close fit to the experimental results. We show from in vitro release experiments that microsphere size has a significant effect on drug release rate. The initial release rate decreased with an increase in microsphere size. In addition, the release profile changed from first order to concave-upward (sigmoidal) as the microsphere size was increased. The mathematical model gave a good fit to the experimental release data. Using the numerical optimization technique, it was possible to achieve desired release profiles, in particular zero-order and pulsatile release, by combining individual microsphere populations at the appropriate proportions. Overall, this work shows that engineering polymeric microsphere populations having predetermined characteristics is an effective means to obtain desired therapeutic drug release patterns, relevant for controlled drug delivery.

High Mach-number compressible flows with heat release are inherently more complicated than incompressible flows due to, among other reasons, the activation of the thermal energy mode. Such flow fields can experience significant fluctuations in density, temperature, viscosity, conductivity and specific heat, which affect velocity and pressure fluctuations. Furthermore, the flow field cannot be assumed to be dilatation-free in high Mach numbers and even in low Mach-number flows involving combustion, or in boundary layers on heated walls. The main issue in these high-speed and highly-compressible flows is the effect of thermal gradients and fluctuations on turbulence. The thermal field has various routes through which it affects flow structures of compressible turbulence. First, it has direct influence through pressure, which affects turbulence via pressure-strain correlation. The indirect effects of thermal fields on compressible turbulence are through the changes in flow properties. The high temperature gradients alter the transport coefficient and compressibility of the flow. The objective of this work is to answer the following questions: How do temperature fluctuations change the compressible flow structure and energetics? How does compressibility in the flow affect the non-linear pressure redistribution process? What is the main effect of spatial transport-coefficient variation? We perform direct numerical simulations (DNS) to answer the above questions. The investigations are categorized into four parts: 1) Turbulent energy cascade and kinetic-internal energy interactions under the influence of temperature fluctuations; 2) Return-to-isotropy of anisotropic turbulence under the influence of large temperature fluctuations; 3) The effect of turbulent Mach number and dilatation level on small-scale (velocity-gradient) dynamics; 4) The effect of variable transport-coefficients (viscosity and diffusivity) on cascade and dissipation processes of turbulence. The findings lead to a better understanding of temperature fluctuation effects on non-linear processes in compressible turbulence. This improved understanding is expected to provide direction for improving second-order closure models of compressible turbulence.

Abstract The interface crack of an IC package is easily existed under vibration, high temperature or collision. Its reliability will be reduced significantly for the existence of the crack. This study, therefore, is to investigate the fracture mechanism of the underfill/substrate interface with different crack length. In this study, mixed mode fracture of the underfill/substrate interface, was investigated by single lap tension test. Based on the load-displacement curve, J integral, energy release rate and stress intensity factor were calculated. Moreover, the relationships among the stress intensity facto KI, KII and phase angle were also derived.

Controlled drug delivery systems deliver drugs at predetermined rates for extended periods. Although there are various types such as capsules, tablets etc, micro and nano spheres are the most commonly used systems. In this study, a set of chitosan-polyvinylpyrrolidone (CH-PVP) microspheres containing different amounts of polyvinylpyrrolidone as semi inter penetrating networks (semi-IPN) were prepared as controlled release systems. Emulsification method was applied for the preparation of microspheres and some of them were conjugated with a monoclonal antibody which is immunoglobulin G (IgG). CH-PVP films were also prepared by solvent casting method with the same composition as in the microspheres and, mechanical and surface properties of the films were examined. Prepared microspheres were characterized by SEM, stereo and confocal microscopes. Some microspheres were loaded with a model chemotherapeutic drug, 5-Fluorouracil (5-FU), and in-vitro release of 5-FU were examined in phosphate buffer solutions (pH 7.4, 0.01 M.) It was shown that for semi-IPN samples release was faster compared to pure CH samples and the total release was achived 30 days for CH:PVP-2:1, CH:PVP-3:1 semi-IPNs and CH microspheres and 27 days for CH:PVP-1:1 semi-IPN microspheres. The antibody conjugated microspheres were targeted to MDA-MB (human causasian breast carcinoma cancer cells and coculture cells in culture medium. For the CH-PVP films, it was obtained that as the amount of PVP increased, hydrophobicity as well as mechanical strength of the system was decreased.

The aim of this project was to design an intelligent controlled release system based on thermoresponsive nanoparticles for cancer therapy and to evaluate the efficiencies of these systems with in vitro cell culture. Poly(Nisopropylacrylamide), an important thermoresponsive polymer, was selected for this study to prepare the responsive nanoparticles. This polymer has an lower critical solution temperature (LCST) of 32 oC, below which it is hydrophilic and above this temperature, it shows hydrophobic behavior. Controlling drug release with this property was the objective of this study. Nanoparticles were prepared by nanoprecipitation method. By using different solvent:non-solvent ratios and polymer concentrations, different samples were prepared. The particle size was decreased when solvent:non-solvent ratio was increased and polymer concentration was decreased. This was found to be related with the solution viscosity. Nanoparticles prepared from polymers prepared with different initiatoraccelarator amounts had significantly different sizes and release rates, and additionally the size of particles prepared from polymers with various crosslinker amounts were decreased with increased croslinker amount. In situ release experiments were performed both below and above polymer&amp / #8216 / s LCST degree. Uncrosslinked nanoparticles demonstrated higher release rate of Celecoxib above LCST. However, there was no significant difference with the crosslinked nanoparticles. Crosslinked and uncrosslinked nanoparticles were tested on Saos-2 cells to assess their toxicity. Both Celecoxib loaded and free crosslinked particles were found to be cytotoxic. Uncrosslinked nanoparticles showed an increased toxicity upon loading with the bioactive agent, Celecoxib. In conclusion, uncrosslinked particles would be a proper drug carrier for cancer therapy with enhanced drug loading.

beta-Bungarotoxin (beta-BuTx), the presynaptic neurotoxin purified from the venom of Bungarus multicinctus, consists of two dissimilar polypeptide subunits. A phospholipase A2 subunit named A chain, and a non-phospholipase A2 subunits named B chain. The A chain and B chain are covalently linked by one disulfide bridge. Although it has been widely accepted that the toxic effect of beta-BuTx is attributed to the disturbance of presynaptic transmitter release, however the inhibition of transmitter release by beta-BuTx is still obscure. Here we investigate the mechanism that mediates facilitation of transmitter release at the neuromuscular junction induced by beta-BuTx, using Xenopus nerve-muscle coculture. Application of beta-BuTx and isotoxins BM12, BM13 led to a marked increase in the frequency of spontaneous synaptic currents (SSCs) after a short period (12~18 min) of latency. The synaptic potentiation induced by these toxins was abolished when Ca2+ in the medium is substituted by Ba2+ (a potent phospholipase A2 inhibitor). Application of PLP-BM12 and PLP-BM13, which have been chemical-modification to lose their PLA2 activity from BM12 and BM13, failed to potentiate the transmitter release.

Historically, the collared peccary (Tayassu tajacu) occurred throughout much of Texas including the northern portion of the Texas Hill Country. Remaining peccary populations were extirpated in much of their former range due to over harvest and habitat loss. In 2004, efforts to restore peccary populations to the Texas Hill Country began when Texas Parks and Wildlife Department biologists translocated 29 collared peccaries into the 2,157 ha, Mason Mountain Wildlife Management Area (MMWMA). I evaluated the success of peccary translocations for mixed and intact family groups by comparing survival, ranges, and dispersal of translocated, radio-tagged peccaries. In addition, I evaluated two release methods (soft versus hard) to determine differences in population demographics. I found that peccary ranges and dispersal patterns did not differ (P > 0.05) between intact and mixed groups or release method (soft versus hard). However, I did find that peccary fidelity to release sites was greater for soft releases of family groups. Individuals from the soft release group dispersed the shortest distance and stayed on MMWMA. Only 2 individuals from the hard releases stayed on MMWMA while the rest (19 individuals) dispersed 4-8 km. Future peccary translocations should emphasize the release method employed and family structure of individuals released to improve translocation effectiveness in establishing populations in target areas.

Contaminated sediments are periodically subjected to resuspension processes during either storm events or due to dredging. In sediments, metals are often contained in insoluble low bioavailability forms. Upon resuspension, however, biogeochemical processes associated with the exposure to more oxic conditions may lead to transformation and release of the metals, giving rise to exposure and risk in the water column. Batch experiments suggested that oxidation of reduced species and corresponding pH decrease were the most importance processes controlling metals release upon sediment resuspension. A mathematical model was implemented to better understand the complex underlying biogeochemical reactions that affect metals release. The model described the metals dynamics and other inter-related important biogeochemical factors well and was successful at predicting the metals release from different sediment reported in the literature. Tidal and other cyclic variations in oxygen, pH and other relevant parameters in the overlying water may also lead to cyclic transformations and release of metals from surficial sediments. In simulated estuarine microcosm experiments, cyclic variations in pH and salinity due to freshwater/saltwater exchange were shown to lead to cyclic variations in metal release. Both pH and salinity were important factors controlling interstitial dissolved metals concentrations, however, in terms of freely dissolved metals concentrations, which have been considered to be more related with toxicity and bioavailability, pH was the single most important parameter. The mathematical model was extended to the conditions of the cyclic behavior in an estuary and successfully described metals release under such conditions. It is believed that the model can be used to predict the metals behavior in other sediments and conditions by model calibration with a similar experimental approach to that used in this study. / text

New smart drugs demand new smart drug delivery systems and also new smart analysis methods for the drug delivery process and material characterization. This thesis contributes to the field by introducing a new electrodynamic approach for studying the drug diffusion proc-esses as well as the formation of a new type of drug delivery systems, the so called mesoporous nano excipients. Drug diffusion processes from different pharmaceutical materials were examined. The transport of charged drug substances was investigated by electrodynamic methods; either as a release process governed by diffusion using the alternating ionic current method or by applying a voltage, sinusoidal or dc, to force the drug ions to move in an electric field. Temperature-dependent drug release from microcrystalline cellulose tablets was examined in order to extract information about the diffu-sion process. Percolation theory was also employed to binary mixtures of an insoluble and electrically insulating matrix material together with a soluble and ionic conducting drug. Further, dielectric spectros-copy was proven to be a powerful method for examining the state of vesicle formation of drug and surfactant molecules in a carbopol gel. Finally, a new potential class of pharmaceutical materials were exam-ined, namely the AMS-n mesoporous materials, showing that the al-ternating ionic current method is powerful both in the study of the synthesis of and in the release process from these.

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